MUTATIONS OF PHOSPHORYLATION SITES IN LAMIN-A THAT PREVENT NUCLEAR LAMINA DISASSEMBLY IN MITOSIS

The nuclear envelope is a dynamic structure that completely disassembles in response to MPF cdc2 activity in mitosis. A key feature of this process is the hyper-phosphorylation of the major structural proteins of the envelope, the nuclear lamins A, B, and C. Two highly conserved serine residues of the lamin protein (Ser-22 and Ser-392 of lamins A and C) are symmetrically positioned 5 amino acids from the ends of the large α-helical domain and are shown in the accompanying paper by Ward and Kirschner to be among four sites phosphorylated during nuclear envelope breakdown. Mutations in Ser-22 and Ser-392 that prevent phosphorylation at these sites block the disassembly of the nuclear lamina during mitosis. We propose a model for the regulation of lamin assembly in which phosphorylation just outside the ends of the α-helical domain controls the assembly dynamics of the lamin coiled-coil dimers. © 1990.